The methylation of fibrinogen with dimethyl sulfate modified the carboxyl groups of aspartic and glutamic acids in the fibrinogen structure. This methylation procedure reduced the negative charges in the fibrinogen and did not result in the modification of other amino acid residues in the protein. Approximately 95 carboxyl groups were methylated in 30 minutes with this method. The action of thrombin on the methylated fibrinogen resulted in the release of both fibrinopeptides - A and B. The electrophoretic mobility of both peptides was less anionic than the thrombin-induced fibrinopeptides from unmodified fibrinogen, indicating that a reduction of negative charge occurred within the peptide structure. Isolation of the fibrinopeptides derived from methylated fibrinogen was accomplished by ion-exchange chromatography and their purity verified by high voltage paper electrophoresis. The rate of release of fibrinopeptide-A from methylated fibrinogen was decreased approximately 30% below the rate of release of peptide-A from unmodified fibrinogen. The Alpha and Gamma chains of fibrinogen undergo cross-linking reactions to Alpha-polymer and Gamma-Gamma-dimer, respectively, under the influence of Factor XIII. When fibrinogen is methylated, Factor XIII no longer produces a Gamma-Gamma-dimer; however, the Alpha-polymer was formed under these same conditions.